Variant 6-29603565-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001470.4(GABBR1):c.2864G>A(p.Arg955Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000233 in 1,587,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

GABBR1
NM_001470.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

Variant links:

Genes affected

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

GABBR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016989112).

BS2

High AC in GnomAd4 at 68 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR1	NM_001470.4 linkuse as main transcript	c.2864G>A	p.Arg955Gln	missense_variant	23/23	ENST00000377034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR1	ENST00000377034.9 linkuse as main transcript	c.2864G>A	p.Arg955Gln	missense_variant	23/23	1	NM_001470.4	P1	Q9UBS5-1

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000217

AC:

AN:

207730

Hom.:

AF XY:

0.000284

AC XY:

AN XY:

112642

show subpopulations

Gnomad AFR exome

AF:

0.000243

Gnomad AMR exome

AF:

0.000288

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000796

Gnomad FIN exome

AF:

0.0000550

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.000385

GnomAD4 exome

AF:

0.000210

AC:

302

AN:

1434950

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

140

AN XY:

711620

show subpopulations

Gnomad4 AFR exome

AF:

0.0000915

Gnomad4 AMR exome

AF:

0.000310

Gnomad4 ASJ exome

AF:

0.0000401

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000367

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000236

Gnomad4 OTH exome

AF:

0.000320

GnomAD4 genome

AF:

0.000447

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000371

Hom.:

Bravo

AF:

0.000691

ESP6500AA

AF:

0.000996

AC:

ESP6500EA

AF:

0.000555

AC:

ExAC

AF:

0.000212

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.2864G>A (p.R955Q) alteration is located in exon 23 (coding exon 22) of the GABBR1 gene. This alteration results from a G to A substitution at nucleotide position 2864, causing the arginine (R) at amino acid position 955 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

.;.;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.025

FATHMM_MKL

Uncertain

0.89

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.017

T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.97

.;.;.;L

MutationTaster

Benign

0.97

D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.80

N;N;N;N

REVEL

Benign

0.29

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.038, 0.023

.;B;.;B

Vest4

0.45

MVP

0.83

MPC

1.4

ClinPred

0.031

GERP RS

3.7

Varity_R

0.14

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over